Dental root surface caries is a cause of tooth loss and disease with aging that will become a major public health problem in the near future. The long-term objective of this research is to develop the basic knowledge needed to develop fluoride formulations for safe-self application by the aging population for root caries prevention. Specific Aims will be: To continue the intraoral studies of fluoride effects on root surfaces; to examine the potential of natural and in vitro produced root caries lesions to remineralize; to determine relationships between the quantity and distribution of lesion mineral and remineralization potential; to evaluate the role of collagen remaining in root lesions on remineralization; and to examine biochemically the proteins that leave and remain in root lesions during demineralization and to determine their potential roles as inhibitors or stimulators of remineralization. Specific histochemical and biochemical methods will be used along with polarizing light microscopic measurement of root lesion histomorphological characteristics. Quantitative microradiographic image analysis will used to determine mineral profiles and total mineral content of root surface lesions during all stages of progression and remineralization. Electron microscopy will be used to determine collagen characteristics. Additional knowledge will be gained of the role of the organic matrix and ground substance components of human root surface tissue and fluoride interactions during demineralization and remineralization. This investigation will determine the potential and feasibility of the reversal and prevention of human dental root caries.